An unusual presentation of takotsubo syndrome in an elderly patient

Abstract Takotsubo syndrome occurs predominantly in women and is usually preceded by acute emotional and/or physical stress. Patients commonly present with chest pain and/or dyspnea. Syncope or out-of-hospital cardiac arrest is a rare presentation. We report an unusual case of takotsubo syndrome in an elderly patient who presented with left facial droop, slurred speech, and syncopal episode. Initial presumed diagnosis was an ischemic stroke/transient ischemic attack. However, the patient was then treated for acute myocardial ischemia/infarction based on abnormal electrocardiogram, elevated cardiac troponin, and unremarkable neurological workup. Eventually diagnosed with takotsubo syndrome. Our case illustrates the importance of prompt identification particularly in the context of atypical presentation and further evaluation to rule out serious causes to mitigate related morbidity and mortality while simultaneously avoiding unnecessary investigations.


INTRODUCTION
Takotsubo syndrome (TTS) was named after the Japanese octopus-trapping pot with a round bottom and narrow neck that resembles the shape of the left ventricle at the end of the systole on a ventriculogram.[1] Also described in the literature as 'apical ballooning syndrome,' 'broken heart syndrome,' and 'stress cardiomyopathy' [2].It accounts for 1-3% of all cases of suspected acute myocardial infarction (AMI).[3] It occurs predominantly in women with a mean age of 58-75 years; however, cases in the literature have also been reported in younger women <50 and males-after physical exertion [1,3].Patients with TTS most commonly present with symptoms like chest pain 75.9% followed by dyspnea 46.9% [4]-that mimic acute coronary syndrome (ACS).Syncope or out-of-hospital cardiac arrest is a rare presentation [5].
Here in, we report an atypical presentation of takotsubo syndrome-as syncope, altered mental status, and facial droop.

CASE REPORT
An 81-year-old female former smoker (60 pack-year) with a history of type 2 diabetes mellitus, cerebrovascular accident, and chronic obstructive pulmonary disease who presented to the emergency department with a history of left facial droop, slurred speech, and witnessed non-mechanical fall "several hours" prior to presentation with no reported head injury.Her home medications included atorvastatin, ticagrelor, and metformin.On arrival, patient was asymptomatic.Her temperature was 98.5 • F, blood pressure was 88/52 mmHg, heart rate was 110/min, and oxygen saturation was 93% on room air.Physical exam was notable for altered level of consciousness (GCS score of 14 due to confusion on best verbal response).Initial cardiac troponin was 2.60 (reference range, <=0.05 ng/ml)] with creatinine level of 2.19 (reference range, 0.60-1.20 mg/dl).Other laboratory results are as shown in Table 1.Electrocardiogram (ECG) on arrival showed minimal ST elevation with inverted T waves in leads V2 and V3 shown in Fig. 1.Initial working diagnoses were stroke/transient ischemic attack, along with acute anteroseptal wall myocardial ischemia/infarction.A computed tomography scan of the head without contrast was done, which revealed no signs of acute intracranial pathology (Fig. 2).Patient received 325 mg of aspirin and started on intravenous unfractionated heparin.Cardiology and Neurology services were consulted.Repeat troponin level was 1.98 ng/ml, which had decreased from 2.60 ng/ml 1-h before.Serial ECGs showed resolution of transient ST elevation and development of bi-phasic inverted Twaves involving V1-V6 Fig. 3 (Panel A).Magnetic resonance imaging of the brain and magnetic resonance angiogram of head & neck were unremarkable.Transthoracic echocardiography (TTE) revealed mid-anteroseptal/apical akinesis with left ventricular ejection fraction (LVEF) of 40-45%-highly suggestive of takotsubo cardiomyopathy.A shared decision was made to postpone cardiac catheterization in the setting of acute kidney injury (AKI) and discontinue heparin drip.Meanwhile aspirin, atorvastatin, and ticagrelor were continued during hospitalization.The hospital course was complicated by heart failure with mild to moderate pulmonary edema and hypoxemia on day-6 due to f luid overload.On days 6-7, her biphasic T-wave evolved into deep symmetric

DISCUSSION
According to literature, the most common presentation of patients with TTS is chest pain and/or dyspnea mimicking ACS, however, our case presented with syncope, left facial droop, and altered mentation.There have been some reported cases of Takotsubo syndrome in the literature with unusual presentation.Arunachalam et al. [6] reported 83-year-old female with extreme thirst as presenting complaint, troponin level of 4.241 ng/ml, Twave inversions in the inferior leads on ECG, and LVEF of 30%.Clark et al. [7] reported a 68-year-old female with acute dyspnea due to status asthmaticus, mildly elevated troponin level with ECG findings of ST segment elevations.Muratsu et al. [8] reported  Table 2. International Takotsubo Diagnostic Criteria (2018) 1) Transient hypokinesis, akinesis, or dyskinesis in the left ventricular presenting as apical ballooning or midventricular, basal, or focal wall motion abnormalities; regional wall motion abnormalities that extend beyond a single epicardial vascular distribution.
2) Preceding of an emotional, physical, or combined trigger, but not always present.
3) New ECG abnormalities (ST-segment elevation, ST-segment depression, T-wave inversion, and QTc prolongation) or modest elevation in cardiac troponin.4) Neurologic disorders (e.g.subarachnoid hemorrhage, stroke/transient ischemic attack, or seizures), as well as pheochromocytoma, may serve as triggers.5) Levels of cardiac biomarkers (troponin and creatine kinase) are moderately elevated with significant elevation of brain natriuretic peptide is common.6) Significant coronary artery disease (CAD) is not a contradiction.7) Patients have no evidence of infectious myocarditis.8) Postmenopausal women are primarily affected population.
Most common complication is mild to moderate heart failure with or without pulmonary edema.Coronary angiography (CAG) with left ventriculography is considered gold standard to rule in or rule out TTS due to the lack of reliable non-invasive diagnostic tools [9,10].To rule out diagnoses, modalities such as cardiac MRI and CCTA are both reliable options.For patients who are at high-risk of complications from CAG, CCTA is recommended.However, for the sub-acute phase, cardiac MRI with late gadolinium enhancement is more helpful, according to Ghadri et al. (Part 2), [10] International Takotsubo Diagnostic Criteria were proposed in 2018 for diagnosing TTS based on International Consensus (Table 2) [10]-differ from the widely known Revised Mayo Clinic Criteria due to the absence of obstructive CAD or angiographic evidence of acute plaque rupture; pheochromocytoma, myocarditis, recent significant head trauma, intracranial bleeding, and hypertrophic cardiomyopathy (HOCM) [9].The differential diagnoses in regard to our case were ischemic stroke/TIA, anteroseptal wall MI, Wallen's syndrome, TTS, and arrhythmogenic right ventricular cardiomyopathy.Nevertheless, a diagnosis of TTS was made given the patient's postmenopausal age, atypical symptoms, new ECG findings, TIA, absence of neurological bleeding, slight elevation in troponin level, mid-anteroseptal/apical akinesis on TTE, improvement of LVEF and resolution of wall motion abnormalities within few weeks.
Treatment is usually supportive care-as there is no established therapy and symptoms resolve within a few weeks.However, initial management is the same as AMI with aspirin, intravenous heparin, and morphine and oxygen if needed, beta-blockers unless contraindicated, serial ECGs, and troponins due to similar presentation [10].Prognosis is usually favorable.Rate of stroke/TIA was reported to be higher (1.7% per patient year) than MI in patients with TTS.The reported recurrence rate was 1.8% per patient-year with a duration range from 25 days to 9.2 years after the first incident.[4] Takotsubo syndrome mimics ACS, making it challenging to distinguish between ACS and takotsubo syndrome based on electrocardiograms and cardiac troponins, especially in cases of atypical presentation.Early cardiac catheterization is an effective way to rule out serious causes, reduce morbidity and mortality, and avoid misdiagnosis in cases where TTS may be mistaken for ACS; thereby, simultaneously avoiding unnecessary investigations.

Figure 2 .
Figure 2. Computed tomography of the head demonstrated diffuse parenchymal volume loss and chronic microvascular changes but no acute intracranial pathology.

Figure 3 .
Figure 3. Follow-up electrocardiograms revealed resolution of ST-elevation with development of diffuse inverted T-wave (blue arrows) in precordial leads (Panel A) that evolved into deep symmetric T-wave inversions (black arrows) in V1-V2 (Panel B).

Table 1 .
Blood work-up on admission and discharge EGFR: Estimated glomerular filtration rate, ESR: Erythrocyte sedimentation rate, GCA: Giant cell arteritis